Recent available instruments allow to record the number of differential somatic cell count (DSCC), representing the combined proportion of polymorphonuclear leukocytes and lymphocytes, on a large number of milk samples. Milk DSCC provides indirect information on the udder health status of dairy cows. However, literature is limited regarding the effect of DSCC on milk composition at the individual cow level, as well as its relation to the somatic cell score (SCS). Hence, the aims of this study were to (i) investigate the effect of different levels of DSCC on milk composition (fat, protein, casein, casein index, and lactose) and (ii) explore the combined effect of DSCC and SCS on these traits. Statistical models included the fixed effects of days in milk, parity, SCS, DSCC and the interaction between SCS × DSCC, and the random effects of herd, animal within parity, and repeated measurements within cow. Results evidenced a decrease of milk fat and an increase in milk fatty acids at increasing DSCC levels, while protein, casein and their proportion showed their lowest values at the highest DSCC. A positive association was found between DSCC and lactose. The interaction between SCS and DSCC was important for lactose and casein index, as they varied differently upon high and low SCS and according to DSCC levels.